Although the cochlear implant is among the most successful of neural prostheses, there remains extreme variability in hearing results enjoyed by implant recipients. Thus open set word recognition scores vary between 0% and over 95%. In addition, the immediate and delayed trauma induced by cochlear implantation is extremely variable and in some cases may be progressive and lead to worsening of the word recognition scores achieved postoperatively. The overall objectives of the proposed research in this grant application are (1) to predict and maximize the word recognition scores in patients who have undergone implantation and (2) to limit the immediate and delayed trauma to the inner ear after cochlear implantation. All of the specific Aims are directed toward one or both of these objectives: Aim 1. Develop, test, and implement patient-specific electro-anatomic models (PSEAMs) and use to identify peripheral anatomic and physiologic factors that limit performance as judged by word recognition scores (overall objective 1). Aim 2. Perform a correlation study between histologic and radiographic reconstruction of intracochlear electrode position in postmortem human temporal bones (overall objectives 1,2). Aim 3. Evaluate the preservation of supporting cells of the organ of Corti as possible candidates as progenitor cells in future regenerative therapy following cochlear implantation in the human (overall objective 2). This Aim will be facilitated greatly by the successful accomplishment of Aim 2, which will allow improved histologic and immunohistochemical studies of these human specimens. Aim 4. Characterize the cellular immune response to cochlear implantation in the human using lymphoid cell markers for T and B cell subsets (overall objective 2). More than 50% of human specimens from patients who in life have received a cochlear implant demonstrate some evidence of cellular immune response which may cause postoperative degenerative changes including fibrosis, new bone formation and cellular loss which may limit the capacity of regenerative techniques. Better characterization of this cellular immune response may provide opportunity for prevention or medical intervention. Aim 5. Evaluate the histopathologic changes in temporal bones from humans with otosclerosis and cochlear implantation (overall objectives 1 and 2). Otosclerosis is extremely common in the human population (approximately 1 in 10 individuals) and has been well documented to cause incomplete or aberrant insertion of electrodes in some cases, and may require alteration of the stimulus strategy. Aim 6 (formerly Aim 7). Continue the accrual of well documented human temporal bones from patients who in life had undergone cochlear implantation (overall objectives 1 and 2). PUBLIC HEALTH RELEVANCE: This grant application proposes research that is based on a unique resource of human temporal bones collected at the Massachusetts Eye and Ear Infirmary including specimens from 59 human subjects who in life had undergone cochlear implantation. The overall purpose and objectives of this research is the development of strategies to (1) predict and maximize word recognition scores for profoundly hearing impaired individuals using the cochlear implant and (2) to limit intraoperative and postoperative trauma to the structures of the inner ear including cells of the organ of Corti that may be critical for successful implantation and also for future forms of therapy such as regeneration of the inner ear.